TY - JOUR
T1 - Increased Ca2+ sensitivity and protein expression of SERCA 2a in situations of chronic beta3-adrenoceptor deficiency
AU - Ziskoven, Christoph
AU - Grafweg, Sabrina
AU - Bölck, Birgit
AU - Wiesner, Rudolf J
AU - Jimenez, Maria
AU - Giacobino, Jean-Paul
AU - Bloch, W
AU - Schwinger, Robert H G
AU - Brixius, Klara
PY - 2007/1/1
Y1 - 2007/1/1
N2 - This study investigated the influence of chronic beta(3)-adrenoceptor deficiency on myocardial function. Therefore, we investigated Ca(2+)-regulatory proteins, SERCA 2a activity, and myofibrillar and mitochondrial function in hearts of wild-type (WT, n=7) and beta(3)-adrenoceptor knockout mice (beta(3)-KNO, n=7). Morphometric heart analysis showed no difference between WT and beta(3)-KNO. No alterations were observed for the protein expression of the ryanodine receptor or phospholamban. However, in beta(3)-KNO mice, protein expression of SERCA 2a and phospholamban phosphorylation were significantly increased. These changes were accompanied by an increased SERCA 2a activity in beta(3)-KNO. Alterations in phospholamban phosphorylation were independent of alterations in beta(1)/beta(2)-adrenoceptor distribution and protein expression of G proteins in beta(3)-KNO. Measurement of myofibrillar Ca(2+) sensitivity showed no difference in the Ca(2+)/force relation for WT and beta(3)-KNO. The same seems to hold true for mitochondrial function since the protein expressions of cytochrome c, uncoupling protein 3 and cytochrome c oxidase subunit IV were similar in WT and beta(3)-KNO. The conclusion is that depression of beta(3)-adrenergic stimulation may modulate the protein expression of SERCA 2a and phospholamban phosphorylation, thereby improving sarcoplasmic reticulum Ca(2+) uptake. Thus, beta(3)-adrenergic depression may be a therapeutic aim in situations of impaired SERCA 2a activity, e.g. for the treatment of heart failure.
AB - This study investigated the influence of chronic beta(3)-adrenoceptor deficiency on myocardial function. Therefore, we investigated Ca(2+)-regulatory proteins, SERCA 2a activity, and myofibrillar and mitochondrial function in hearts of wild-type (WT, n=7) and beta(3)-adrenoceptor knockout mice (beta(3)-KNO, n=7). Morphometric heart analysis showed no difference between WT and beta(3)-KNO. No alterations were observed for the protein expression of the ryanodine receptor or phospholamban. However, in beta(3)-KNO mice, protein expression of SERCA 2a and phospholamban phosphorylation were significantly increased. These changes were accompanied by an increased SERCA 2a activity in beta(3)-KNO. Alterations in phospholamban phosphorylation were independent of alterations in beta(1)/beta(2)-adrenoceptor distribution and protein expression of G proteins in beta(3)-KNO. Measurement of myofibrillar Ca(2+) sensitivity showed no difference in the Ca(2+)/force relation for WT and beta(3)-KNO. The same seems to hold true for mitochondrial function since the protein expressions of cytochrome c, uncoupling protein 3 and cytochrome c oxidase subunit IV were similar in WT and beta(3)-KNO. The conclusion is that depression of beta(3)-adrenergic stimulation may modulate the protein expression of SERCA 2a and phospholamban phosphorylation, thereby improving sarcoplasmic reticulum Ca(2+) uptake. Thus, beta(3)-adrenergic depression may be a therapeutic aim in situations of impaired SERCA 2a activity, e.g. for the treatment of heart failure.
KW - Animals
KW - Calcium
KW - Calcium-Binding Proteins
KW - Echocardiography
KW - GTP-Binding Proteins
KW - Gene Expression
KW - Heart Failure
KW - Immunoblotting
KW - Male
KW - Mice
KW - Mice, Knockout
KW - Mitochondrial Proteins
KW - Myofibrils
KW - Phosphorylation
KW - Receptors, Adrenergic, beta-3
KW - Ryanodine Receptor Calcium Release Channel
KW - Sarcoplasmic Reticulum
KW - Sarcoplasmic Reticulum Calcium-Transporting ATPases
KW - Signal Transduction
U2 - 10.1007/s00424-006-0137-7
DO - 10.1007/s00424-006-0137-7
M3 - Journal articles
C2 - 17021799
SN - 0031-6768
VL - 453
SP - 443
EP - 453
JO - Pflügers Archiv : European journal of physiology
JF - Pflügers Archiv : European journal of physiology
IS - 4
ER -